IMARK. Network for image-based biomarker discovery and evaluation 01/01/2021 - 31/12/2026

Abstract

IMARK capitalizes on the deeply rooted expertise in biomedical imaging at the University of Antwerp to push the boundaries of precision medicine. By resolving molecular and structural patterns in space and time, IMARK aims at expediting biomarker discovery and development. To this end, it unites research groups with complementary knowledge and tools that cover all aspects of imaging-centred fundamental research, preclinical validation and clinical evaluation. IMARK harbours high-end infrastructure for electron and light microscopy, mass spectrometry imaging, magnetic resonance imaging, computed tomography, positron emission tomography and single-photon emission computed tomography. Moreover, IMARK members actively develop correlative approaches that involve multiple imaging modalities to enrich information content, and conceive dedicated image analysis pipelines to obtain robust, quantitative readouts. This unique blend of technologies places IMARK in an excellent position as preferential partner for public-private collaborations and offers strategic advantage for expanding the flourishing IP portfolio. The major application fields of the consortium are neuroscience and oncology. With partners from the Antwerp University Hospital and University Psychiatric Centre Duffel, there is direct access to patient data/samples and potential for translational studies.

Researcher(s)

Research team(s)

MIMICRY - Modulating Immunity and the Microbiome for effective CRC. 01/01/2021 - 31/12/2024

Abstract

A fundamentally important biological question is how our bodies maintain a critical balance between inflammation and immune tolerance, and how this may be modified or evaded by cancers. The human colon, a tissue where many inflammatory diseases and cancers arise, performs this balancing act basally in the presence of dietary antigens and the normal microbiome. Within this homeostatic state, colorectal polyps and colorectal cancer (CRC) arise and can evade clearance by the immune system despite treatment by immune checkpoint inhibitors. We hypothesize that these pre-malignant lesions subvert the default tolerogenic state of the colon and induce additional immunosuppressive mechanisms. Deciphering the complex interaction between the epithelium, immune system and microbiome requires a talented group of researchers with complementary expertise. The unique composition of this 'MIMICRY' iBOF consortium aims to combine human samples, state-of-the-art immunology, novel tools, and in vivo mouse models to study the multi-factorial aspects of colorectal cancers. These will help develop novel immunotherapeutic strategies.

Researcher(s)

Research team(s)

Versatility by processing: proprotein convertases and their role in expanding neuropeptidergic diversity. 01/11/2020 - 31/10/2023

Abstract

Neuropeptides are signaling molecules used by all Metazoan nervous systems to control physiology and behavior. They are produced by extensive processing from larger protein precursors. In mammals, examples are known where this processing can lead to distinct sets of neuropeptides in different tissues, due to differential expression of the proprotein convertases; a family of proteases responsible for cleavage of the protein precursors. However, apart from these few examples, little is known on how extensive differential processing is, and how proprotein convertases might be responsible for expanding signaling diversity in the nervous system. Via this project proposal, I am to address ignorance regarding this level of control, and provide detailed information on the prevalence and functional impact of differential processing. To unveil fundamental principles of differential neuropeptide processing, I intend to use peptidomics on the model organism Caenorhabditis elegans, an organism for which I can also map the differentially processed neuropeptides and their proprotein convertases precisely to the individual cells or tissues where these are produced. This information will guide functional studies, where I aim to unveil the physiological impact of differential neuropeptide processing. Overall, this work aims to provide insight into how differential processing can functionally diversify the neuropeptide arsenal, as generated from a fixed set of precursors.

Researcher(s)

Research team(s)

Comprehensive Liquid Chromatography - Ion Mobility - Quadrupole-Time-of-Flight Mass Spectrometry for innovative metabolomics. 01/05/2018 - 30/04/2021

Abstract

The requested infrastructure (comprehensive liquid chromatograph-ion mobility-quadrupole time of flight mass spectrometer LCxLC-IM-QTOFMS) combines several state-of-the-art technologies into one platform which aims at bringing metabolomics research to the next level. As such, the infrastructure will deliver a combined five-dimension separation and detection technology, the first of its kind in Belgium. This instrument will be dedicated to metabolomics research, the science of endogenous metabolites in cells, tissues or organisms. The infrastructure will be able to optimally separate, detect and identify the very broad and complex chemical space of metabolites ranging from very polar (e.g. amino acids) to non-polar (e.g. lipids and hormones) at low nanomolar concentration range. Within UA, there is a growing need to combine the currently scattered efforts in metabolomics, an Emerging Frontline Research Domain in the UA research scene. Research ranges from drug discovery (mode of action and pharmacokinetic profiling), biomarker and toxicity studies to advanced data-analysis and systems biology approaches, but a dedicated metabolomics infrastructure to strengthen these studies is currently missing. As such, the investment in a core facility together with the gathering of nine research groups from five departments and two faculties would centralize the metabolomics research. This will position UA as a key player in the academic metabolomics research in the BeNeLux and worldwide.

Researcher(s)

Research team(s)

Dendritic remodeling as fuel for axonal regeneration. 01/10/2017 - 30/09/2019

Abstract

In this project we aim at shedding light on how dendritic remodeling processes contribute to neuronal survival and axonal regeneration in the injured teleost fish CNS and at investigating whether modulation of underlying molecules or pathways can lead to increased neuroprotection or regeneration in the mammalian CNS. Thereto, a combination of state-of-the-art molecular, biochemical, morphological, functional and behavioral tools will be used in two vertebrates with different strengths: zebrafish and mice.

Researcher(s)

Research team(s)

MALDI Mass Spectrometry Imaging (MALDI-MSI): Bridging proteomics and imaging. 01/05/2016 - 30/04/2020

Abstract

The instrument acquired in this project is a matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometer capable of mass spectrometry imaging (MSI). This technique is especially developed for the identification of biomolecules in a manner that retains cytological and histological patterning. This novel technical process, abbreviated to MALDI-MSI represents an interesting and extremely productive intersection between mass spectrometric and imaging platforms. Therefore, this grant is bridging 3 University of Antwerp CORE facilities (Center for Proteomics, Bio-Imaging lab and the Biomedical Microscopic Imaging Core). Using this MALDI-MSI platform, multiple research groups, brought together by a common interest in investigating molecular damage associated with aberrant aging mechanisms, will be able to identify a diverse range of small molecules (peptides and metabolites) as well as larger proteins directly on tissue slides, preserving the topological, histological and cytological data. This is not possible with routine proteomics and metabolomics technologies nor with advanced imaging techniques.

Researcher(s)

Research team(s)

    Predicting immunotherapy response in elderly non-small cell lung cancer patients by zooming into protein/peptide expression patterns at the tumor cell - immune cell interaction border. 01/01/2016 - 31/12/2019

    Abstract

    Lung cancer still remains one of the most deadliest cancers worldwide, with over 14 million new diagnoses and 8.2 million cancer-related deaths in 2012. Since only a minority of the patients respond to chemotherapy and targeted therapies, immunotherapy might be a valid alternative. The major goal of these therapies is to activate the tumor-deleting characteristics of the immune system. It is known however, that the immune system activity diminishes with age. Therefore, an important question remains whether elderly lung cancer patients would benefit from these immunotherapies. In this project, we will characterize which immune-related proteins and peptides are expressed within the lung tumor microenvironment of elderly patients, at places where immune cells and tumor cells co-reside. This will provide us insights to which factors are important for the maintenance of the immune-suppresive microenvironment. Further comparison of protein/peptide expression patterns of different elderly lung cancer patients might deliver a protein/peptide panel, able to predict which subgroup of patients might benefit from the immunotherapy, thereby optimizing therapy response, minimizing therapy-related toxicity and improving quality of life.

    Researcher(s)

    Research team(s)

    Dendritic remodeling as fuel for axonal regeneration. 01/10/2015 - 30/09/2017

    Abstract

    As adult mammals lack the capacity to regenerate damaged neurons, dysfunction of the central nervous system (CNS) after brain injury or in neurodegenerative diseases increasingly impairs life quality in our aging society. Despite intensive research efforts, induction of regeneration and subsequent functional recovery of the injured mammalian CNS remains a challenge, which makes the search for new regeneration-inducing molecules essential. In this project we aim to shed light on how dendritic shrinkage/remodeling contributes to neuronal survival and axonal regeneration and to identify and further characterize molecules and pathways that contribute to neuroprotection and regeneration. Hereto, we will use state-of-theart molecular, biochemical, morphological, functional and behavioral tools in the visual system of two vertebrates with different strengths, zebrafish and mice. As zebrafish have a very high regenerative potential, they provide a unique model for the analysis and identification of crucial molecules and signaling pathways contributing to a successful axonal regeneration after CNS injury. Subsequent validation of our findings in mice allows the identification of key regulatory molecules for improved regeneration in mammals. This study proposes to advance our knowledge on the molecules and mechanisms underlying axonal outgrowth, which is highly needed to establish successful and novel regenerative therapies promoting neural repair.

    Researcher(s)

    Research team(s)

    Micropeptides as a new class of bio-active peptides in higher eukaryotes. 01/01/2014 - 31/12/2017

    Abstract

    The objective of this project is to discover new micropeptides in Drosophila melanogaster and Mus musculus. This project combines both wet-lab and theoretical (in silico) experiments. Ribosome profiling experiments will elucidate the translated mRNA of both model organisms. Furthermore different MS-based peptidomics strategies will be performed attempting to confirm the discovery of the micropeptides from the aforementioned NGS experiment. In parallel, a peptide prediction algorithm will be devised based on known and new micropeptide sequence characteristics and their conservation. Finally, the discovered micropeptides will be tested for activity on a panel of different cell lines.

    Researcher(s)

    Research team(s)